The present invention is directed to certain 2- substituted perhydro-1H-pyrido[1,2-a]pyrazines which are depicted by the formula (I) as defined below, and to pharmaceutical compositions comprising these compounds, and a method of treating psychotic diseases therewith.
Commonly-owned U.S. patent application No. 07/661,791, filed Feb. 27, 1991 U.S. Pat. No. 5,157,034, the disclosure of which is herein incorporated by reference, is directed to both racemic and optically active perhydro-1H-pyrido[1,2-a]pyrazines having the formula ##STR2## wherein Z is H or Cl;
Y is O or S; PA1 n is 1, 2, 3 or 4; and when PA1 R.sup.2 is hydrogen, methyl, hydroxyl, alkoxy and acyloxy; PA1 R.sup.3 is hydrogen, hydroxyl, and methoxy; PA1 R.sup.4 is hydrogen, methyl and oxo; and PA1 X is S, SO, and SO.sub.2.
L and X are taken together are: ##STR3## where Y.sup.1 is CH.sub.2, S, O or NH; Y.sup.2 and Y.sup.3 are taken separately and Y.sup.2 and Y.sup.3 are each independently hydrogen or methyl, or Y.sup.2 and Y.sup.3 are taken together and are (CH.sub.2).sub.q ; p is 1 or 2, q is 2, 3, 4 or 5; and r is 0 or 1.
U.S. Pat. No. 4,956,368, issued Sep. 11, 1990 discloses various metabolites and prodrug formulations of 8-[4-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]butyl]-8-azaspiro(4,5)deca ne-7,9-dione which are particularly useful in the treatment of psychotic disorders, especially derivatives thereof which have been oxygenated at specified sites about the original structure, rearranged compounds, and prodrug formulations of these species. One particularly desired group of compounds have the general formula ##STR4## where: R.sup.1 is hydrogen, hydroxyl, alkoxy, acyloxy and oxo;
Perhydro-1H-pyrido[1,2-a]-pyrazines of the formula ##STR5## wherein X.sup.a is N or CH and L.sup.a represents one of certain pyrazolo, triazolo, tetrazolo or cyclic imido radicals have been reported to possess useful anxiolytic activity, Bright and Desai, International Application published under the PCT as publication No. WO 90/08144.
A variety of compounds are reported to be in possession of neuroleptic activity useful in the treatment of psychotic diseases. These include piperidine derivatives of the formula ##STR6## wherein t is 1 or 2, Ar is naphthyl or one of a variety of bicyclic heteroaryl groups, including benzisothiazoyl, and X.sup.b and Y.sup.b together with the attached phenyl group form a similar such bicyclic heteroaryl group (Lowe, III et al., U.S. Pat. No. 4,831,031); and compounds of the formula ##STR7## wherein Q represents certain bicyclic heteroaryl groups, Alk is alkanediyl X.sup.c represents, O, S, NH, or substituted NH (Kennis et al., U.S. Pat. No. 4,957,916).